Since 1978 the Center for Research on the Etiology and Treatment of Alcohol Dependence (UConn ARC) has been devoted to a systematic exploration of the alcohol dependence syndrome, its etiology, patterning and treatment. This application requests five years of continued funding for the Center's research programs on vulnerability to alcoholism, mechanisms of alcohol dependence, and promising treatment interventions. Component 9001 (Scientific Core) describes the UConn ARC's organizational framework, quality control mechanisms, and core research laboratories. Component 21 describes a study of vulnerability that will examine the relationship of family history, antisocial personality disorder and gender to measures of cognitive functioning. This study will pursue new findings on the role of frontal lobe functioning in risk for alcoholism. Component 23 (Protracted withdrawal) will study electrophysiological and subjective features of protracted withdrawal, including GABA/BDZ receptor sensitivity. Component 16 proposes two studies of psychological mechanisms of dependence in abstinent alcoholics (Study A) and nondependent heavy drinkers (Study B). Components 24 and 25 are concerned with the treatment of alcohol dependence, building on promising results obtained during the current grant period with new pharmacotherapies. One study (Naltrexone treatment) will investigate subjective and physiological responses to naltrexone (a narcotic antagonist found to prevent relapse in abstinent alcoholics), and its effects on voluntary alcohol consumption in a laboratory model. A second component (Randomized clinical trial of gepirone) will evaluate the safety and efficacy of a new serotonin agonist as a treatment for alcohol dependence. In addition to the major research components, the application includes an ambitious pilot studies program.